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Stéphane Giraudier

Publications and source records attributed to Stéphane Giraudier.

2 recordsLinked to original sources

Hematopoiesis as a continuum: from stochastic compartmental model to hydrodynamic limit

We consider a multiscale stochastic compartmental model with three types of cells (stem cells, immature cells and mature cells) which combines cell proliferation and cell differentiation. We derive a hydrodynamic limit when the number of immature compartments goes to infinity obtaining a partial differential equations system with boundary conditions, modelling hematopoiesis as a continuum. We assume that proliferation and differentiation are regulated and let the corresponding rates depend on the number of mature cells. This leads us to model the dynamics of the population by a Markov process in continuous time and discrete space, which does not satisfy the branching property. We prove the convergence in law of the stem and mature cells population size processes and of the empirical measures of the immature cells dynamics, conveniently rescaled, to the unique triplet involving coupled functions and a measure, which are solutions of a deterministic measure valued equation with boundary dynamics. The cell differentiation induces a transport term in space and the main difficulty comes from the boundary effects coming from stem and mature cells. We also prove that the limiting measure admits at each time a density with respect to Lebesgue measure and can be characterized as solution of a partial differential equation.

math.PR↗

Classical JAK2V617F+ Myeloproliferative Neoplasms emergence and development based on real life incidence and mathematical modeling

Mathematical modeling allows us to better understand myeloproliferative neoplasms (MPN), a group of blood cancers, emergence and development. We test different mathematical models on an initial cohort to determine the emergence and evolution times before diagnosis of JAK2V617F+ classical MPN (Polycythemia Vera (PV) and Essential Thrombocythemia (ET)). We consider the time before diagnosis as the sum of two independent periods: the time (from embryonic development) for the JAK2V617F mutation to occur, not disappear and enter proliferation, and a second time corresponding to the expansion of the clonal population until diagnosis. We prove that the rate of active mutation occurrence increases exponentially with age following the Gompertz model rather than being constant. We find that the first tumorous cell takes an average time of $63.1 \pm 13$ years to appear and start proliferation. On the other hand, the expansion time is constant: $8.8$ years once the mutation has emerged. These results are validated in an external cohort. Using this model, we analyze JAK2V617F ET versus PV, and obtain that the time of active mutation occurrence for PV takes approximately $1.5$ years more than for ET to develop, while the expansion time was similar. In conclusion, our age-dependent approach for the emergence and development of MPN demonstrates that the emergence of a JAKV617F mutation should be linked to an aging mechanism, and indicates a $8-9$ years period of time to develop a full MPN.

q-bio.PE↗